The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa
The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa
复制标题
SiaA/B/C/D 信号网络调节铜绿假单胞菌生物膜的形成。
DOI：
10.15252/embj.2019103412
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发表时间：
2020-03-16
期刊：
影响因子：
11.4
通讯作者：
Liang, Haihua
中科院分区：
文献类型：
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作者：
Chen, Gukui;Gan, Jianhua;Liang, Haihua
细菌环状-DI-GMP（C-DI-GMP）的产生与生物膜发育以及从急性感染转向慢性感染有关。在铜绿假单胞菌中，二烷基酸环化酶（DGC）SIAD和磷酸酶SIAA被共转录为SiaABCD操纵子的一部分，对于细胞聚集至关重要。但是，该操纵子的详细功能及其成分基因之间的关系尚不清楚。在这里，我们证明了SiaABCD操纵子编码的信号网络，该信号网络调节SIAD酶活性以控制生物膜和聚集体形成。通过蛋白质 - 蛋白质相互作用，SIAC促进了SIAD二甘氨酸酸环化酶活性。生化和结构数据表明，SIAB是一种不寻常的蛋白激酶，可磷酸化SIAC，而SIAA磷酸酶可以脱磷酸化SIAC。 SIAC的磷酸化状态对于它与SIAD的相互作用至关重要，SIAC的相互作用将打开或关闭SIAD的DGC活性并调节C-DI-GMP水平以及随后的毒力表型。总的来说，我们的数据提供了对与慢性感染相关的DGC活性调节的分子机制的见解，这可能有助于抗菌药物的发展。
Bacterial cyclic-di-GMP (c-di-GMP) production is associated with biofilm development and the switch from acute to chronic infections. In Pseudomonas aeruginosa, the diguanylate cyclase (DGC) SiaD and phosphatase SiaA, which are co-transcribed as part of a siaABCD operon, are essential for cellular aggregation. However, the detailed functions of this operon and the relationships among its constituent genes are unknown. Here, we demonstrate that the siaABCD operon encodes for a signaling network that regulates SiaD enzymatic activity to control biofilm and aggregates formation. Through protein-protein interaction, SiaC promotes SiaD diguanylate cyclase activity. Biochemical and structural data revealed that SiaB is an unusual protein kinase that phosphorylates SiaC, whereas SiaA phosphatase can dephosphorylate SiaC. The phosphorylation state of SiaC is critical for its interaction with SiaD, which will switch on or off the DGC activity of SiaD and regulate c-di-GMP levels and subsequent virulence phenotypes. Collectively, our data provide insights into the molecular mechanisms underlying the modulation of DGC activity associated with chronic infections, which may facilitate the development of antimicrobial drugs.